(SIRVE comes from the Spanish word servir, to serve. Sirve? used as a question means, Does it work?) This study brings together a team of investigators from diverse disciplines to address the problem of low rotavirus vaccine performance in low and middle income countries (LMICs). While the majority of the child deaths due to rotavirus occur in LMICs, currently-licensed rotavirus vaccines are less effective and have a shorter duration of protection in LMICs as compared to high income countries. A growing body of evidence shows that LMIC infants mount a blunted immune response to the rotavirus vaccines; we expect that this weak response may then wane to non-protective levels in the second year of life. One novel explanation for decreased immunogenicity is inhibition of the oral rotavirus vaccines by breast milk. Preliminary data provided by co-investigator, Baoming Jiang, show that breast milk from LMIC mothers has high rotavirus-specific IgA and is able to inhibit rotavirus vaccine activity in vitro. The propose study takes this laboratory finding to the translational realm by evaluating the effect of a strategic breastfeeding withholding intervention on immunogenicity to the pentavalent rotavirus vaccine in Nicaragua. We propose a randomized control trial of 540 lactating mother-infant pairs to compare the effect of withholding breastfeeding 11/2 hours before and 1 hour after pentavalent rotavirus vaccine administration (intervention) to routine breastfeeding (control) on the frequency of IgA seroconversion to the vaccine in infants. We hypothesize that intervention group infants will have a higher frequency of seroconversion as compared to control group infants. Coupled with the trial, we propose a careful evaluation of changes in breastfeeding patterns or maternal attitudes towards breastfeeding as a result of the intervention. This risk evaluation is necessary to inform the implementation step if the intervention is found to be efficacious. Finally, we plan to address the problem of short duration of rotavirus vaccine protection by preparing for a future clinical trial of booster dose administration. We will collect and analyze sera from immunized children until 18 months of age to describe the kinetics of long-term immunogenicity to the pentavalent rotavirus vaccine . These data will be used to potentially justify and inform the timing of booster dose administration for such a trial. Separately, these data will allow us to assess the long-term effect of the strategic breastfeeding withholding intervention. We propose to conduct the study in Leon, Nicaragua, through the Center for Infectious Disease Research at the University of Nicaragua, Leon, where collaborator Felix Espinoza previously coordinated the field trials of the monovalent rotavirus vaccine in Nicaragua. A pilot study conducted with 80 mother-infant pairs confirms the feasibility of recruitment goals, community follow-up and specimen collection, and laboratory analysis at the CDC's Viral Gastroenteritis Laboratory. Finally, with the assistance of our CDC collaborators, we will maximize the public health impact of the study findings through planned dissemination with international health policy agencies.